2814 - A Pilot Study to Detect Inflammatory Biomarkers of Pneumonitis in Exhaled Breath during Chemoradiotherapy for Stage III Non-Small Cell Lung Cancer

R. T. Hughes¹, K. E. Reno¹, B. Levine², A. C. Bishop³, J. Willey¹, and M. Farris⁴; ¹Department of Radiation Oncology, Wake Forest University School of Medicine, Winston Salem, NC, ²Department of Social Sciences and Health Policy, Wake Forest University School of Medicine, Winston Salem, NC, ³Department of Internal Medicine, Section of Molecular Medicine, Wake Forest University School of Medicine, Winston Salem, NC, ⁴Department of Radiation Oncology, Wake Forest University School of Medicine, Winston-Salem, NC

Purpose/Objective(s): Radiation pneumonitis (RP) is a challenging toxicity for patients with non-small cell lung cancer (NSCLC) treated with chemoradiotherapy (CRT). Symptomatic RP can substantially affect quality of life and delay or even preclude consolidative immunotherapy. Exhaled breath, collected noninvasively during CRT using a simple device, has been found to contain molecular inflammatory biomarkers that may be useful in predicting RP, but this has not been studied in patients with stage III NSCLC treated with CRT. Materials/

Methods: This single-arm pilot study (NCT04040244) enrolled adults with stage III NSCLC treated with definitive CRT (60 Gy) who were able to tolerate exhaled breath collection. Patients taking systemic corticosteroids or antibiotics were excluded, as were patients planned for thoracic re-irradiation. CRT with consolidative immunotherapy was performed per standard of care. Exhaled breath condensate (EBC) and serum samples were collected at baseline, 2- and 6-wks during CRT and 1-mo post-CRT. EBC was collected using the RTube™ collection device. TGF-B1, IL-1a, IL-6, and IL-10 concentration (pg/mL) were measured in the available EBC and serum samples. The study was closed to accrual due to the ongoing risks of collecting exhaled breath during the COVID-19 public health emergency. In this exploratory analysis of collected samples, unadjusted mean biomarker levels are described over time. We used contrasts derived from repeated measures mixed models with a random subject effect (timepoint was treated categorically) to determine significance of change in biomarker levels across different time points.
Results: A total of 16 patients were enrolled. EBC and serum samples were available in 9 patients at baseline, 8 at CRT week 2, 7 at CRT week 6, and 7 at 1-mo post-CRT. Measurable EBC biomarker levels were present in 95.4% of 306 available samples, while 97.8% of 268 serum samples had measurable levels. Mean concentrations of each biomarker at each time point are shown in the Table. There were no significant changes in any of the EBC biomarkers over time, nor in 3 of the 4 serum markers. Serum TGF-B1 showed significant change from baseline to the two later timepoints (both comparisons p<0.01). None of the Spearman correlations of the EBC biomarker levels with the corresponding biomarker levels were statistically significantly different from zero.
Conclusion: Exhaled breath-based analysis of RP-associated biomarkers is feasible with the majority of available samples having measurable levels of substrate. Additional study of EBC-based analyses for RP risk stratification during CRT for NSCLC is warranted.

Abstract 2814 – Table 1

	TGF-B1 Breath	TGF-B1 Serum	IL-1a Breath	IL-1a Serum	IL-6 Breath	IL-6 Serum	IL-10 Breath	IL-10 Serum
Baseline	80.88	5403.06	2.34	11.18	4.75	18.03	139.85	33.29
Week 2 CRT	80.98	4700.07	0.88	3.99	5.34	20.11	144.54	35.69
Week 6 CRT	86.59	3007.08	2.96	3.44	6.52	23.73	140.32	32.63
1-month post CRT	100.46	2819.13	3.61	4.84	6.42	21.11	142.38	31.99